Oral Irritation Assessment of Electronic Liquids using an In-Vitro Oral Testing Model

M. Aragon, A. Sharavanthi Pidathala, D. Sheehan, Gertrude-Emilia Costin

While data are still being collected and analyzed, there were at least 1,300 accidental electronic liquid (e-liquid) exposures reported as of 2013. Deaths have occurred as a result of ingestion of e-liquid with the effects being attributed primarily to nicotine.

The Food and Drug Administration (FDA) sought to regulate e-liquid through the Tobacco Control Act passed in 2009. In 2014, the FDA issued its “Deeming” proposals for public comments, which covered e-liquid manufacturing; the Final Rule giving the FDA authority to regulate e-liquids was released on May 5th, 2016.

This study investigated the oral irritation of 3 different formulations of e-liquid using an in-vitro time course assay in the reconstructed tissue model EpiOral™ (MatTek Corporation, Ashland, MA, USA). All products were from the same manufacturer, contained 1.2% nicotine and differed only in their flavorings.

The e-liquids were tested neat in duplicate tissues. Tissue viability was measured using the vital dye MTT at 15 minutes, 30 minutes, 1 hour, 2 hours, and 16 hours. The ET50 values (representing the exposure time which reduces the tissue viability by 50%) were calculated and used to rank-order the irritation potential of the products. The ET50 values were 4.9h, 6.0h, and >16h, respectively, for the 3 products tested. The results of this study highlight the applicability of the EpiOral™ model in evaluating the oral irritation potential of a variety of e-liquid formulations. Further work will be performed with the culture medium to analyze the inflammatory profile of e-liquids via cytokine analysis.


e-liquids, electronic cigarettes (e-cigarettes), vaping, EpiOral (ORL-200), inter-lot reproducibility, oral irritation

Materials Tested

nicotine, e-cigarettes

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